CA224 (Compound 1) is a selective and orally active Cdk4–cyclin D1 inhibitor with an IC50 of 6.2 µM. CA224 induces cell apoptosis and shows antitumor activity [1].
In Vivo, CA224 (Compound 1) (100 mg/kg; i.p.; once a day for 9 days) shows significant tumor growth inhibition without obvious toxicity[1].
In Vitro, CA224 (Compound 1) (48 h) shows antiproliferation activity against human cancer cell lines[1]. CA224 (18-48 h) blocks the growth of cancer cells at G0/G1 and G2/M phase of the cell cycle, and selectively kills SV40 large T-antigen transformed normal mouse embryonic liver cells (BNL SV A.8)[1][2]. CA224 (0-4 µM, 30 min) inhibits tubulin polymerization and enhances the depolymerization of stabilized tubulin protein[1]. CA224 (0-72 h) induces cell apoptosis in cancer cells[1]. CA224 (10 μM) shows 50%, 14%, 51% and 19% inhibition of CYP3A4, CYP2D6, CYP2C9, and CYP2C19, respectively[1].
References:
[1]. Sachin Mahale, et al. Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization: evaluation of in vitro and in vivo anticancer activity. J Med Chem. 2014 Nov 26;
[2]. Sachin Mahale, et al. CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4272-8.
In Vivo, CA224 (Compound 1) (100 mg/kg; i.p.; once a day for 9 days) shows significant tumor growth inhibition without obvious toxicity[1].
In Vitro, CA224 (Compound 1) (48 h) shows antiproliferation activity against human cancer cell lines[1]. CA224 (18-48 h) blocks the growth of cancer cells at G0/G1 and G2/M phase of the cell cycle, and selectively kills SV40 large T-antigen transformed normal mouse embryonic liver cells (BNL SV A.8)[1][2]. CA224 (0-4 µM, 30 min) inhibits tubulin polymerization and enhances the depolymerization of stabilized tubulin protein[1]. CA224 (0-72 h) induces cell apoptosis in cancer cells[1]. CA224 (10 μM) shows 50%, 14%, 51% and 19% inhibition of CYP3A4, CYP2D6, CYP2C9, and CYP2C19, respectively[1].
References:
[1]. Sachin Mahale, et al. Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization: evaluation of in vitro and in vivo anticancer activity. J Med Chem. 2014 Nov 26;
[2]. Sachin Mahale, et al. CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4272-8.